The effect of TNF and other cytokines on the release of 72 KD (MMP-2) & 92 KD type IV collagenases (MMP-9) from monocytes was evaluated. The release of MMP-9 from THP-1 cells, a human monocytic cell line, was increased by 0.04 - 25 ng/ml TNF (for 18 hours) in a concentration-dependent manner while that of MMP-2 was only slightly increased in the presence of high concentrations of TNF (equal to or greater than 500 ng/ml). TNF also increased the release of MMP-9 from human primary monocytes. IL-1, like TNF, mainly enhanced the release of MMP-9. The effect of TNF was inhibited by anti-TNF but not anti-IL-1 antibodies, while that of IL-1 was inhibited by anti-IL-1 but not anti-TNF antibodies. IL-6 (25 ng/ml) slightly potentiated the release of MMP-9 but not MMP-2 from THP-1 cells. The potentiating effect of IL-6 was diminished by anti-IL-6 and anti-TNF but not anti-IL-1 antibodies, while the effects of TNF and IL-1 were not altered by anti-IL-6 antibodies. Other cytokines such as IL-4 (up to 25 ng/ml) and IFN-gamma (up to 20 ng/ml) had little effect on the release of MMP-2 or MMP-9. Incubation of the THP-1 cells with TNF in the presence of plasmin or addition of TNF to cells in higher density (1.5 x 10(5) cells/ml) induced the release of an 84 KD gelatinase thought to be the active form of MMP-9. These results indicate that TNF, IL-1, and IL-6 potentiate the collagenolytic activity of monocytes and the potentiating effect of TNF is not mediated via IL-1 or vice versa, while that of IL-6 is mediated at least in part via TNF.